Platinum Coordination Complexes
Information about Platinum Coordination Complexes
The platinum coordination complexes are a group of antineoplastic agents that are usually classified as alkylating agents, but which have distinctive features. Their anticancer activity appears to relate to the cross linking of DNA molecules in a fashion similar to standard alkylating agents. The DNA adducts formed by the platinum-containing complexes inhibit DNA replication and lead to strand breaks and miscoding, thereby eliciting apoptosis as well as inhibition of RNA and protein synthesis.
Mechanism of action of Platinum Coordination Complexes
The first of the platinum coordination complex with alkylating activity introduced into clinical medicine was cisplatin. Cisplatin was first described in 1845 as Peyrone's salt and in 1893 its chemical structure was elucidated. In the 1960s, cisplatin was shown to have anticancer activity in vitro and in vivo. Upon this discovery, multiple platinum containing compounds were synthesized and studied for anticancer activity in screening assays. Cisplatin was found to have the most potency. Cisplatin (Platinol) was approved for use in the United States in 1978 and became an important component of therapies of ovarian, testicular, bladder, head and neck, easophagus, lung and colon cancer. Carboplatin (Paraplatin) was approved for treatment of ovarian cancers in 1989 and oxaliplatin (Eloxatin) for colorectal cancer in 2003. The platinum coordination complexes have similar antineoplastic activities and are used largely for advanced cancer and in combination with other agents.
Side effects of Platinum Coordination Complexes
All must be given by intravenous infusion, and all are associated with significant renal, intestinal, bone marrow and neurologic toxicities. The platinum-containing agents are also mutagenic, teratogenic and carcinogenic, and their use has been associated with an increased risk of secondary leukemias.
Liver safety of Platinum Coordination Complexes
Cisplatin and carboplatin are rare causes of liver injury, while oxaliplatin has been associated with a high rate of histological changes when used prior to hepatic resection of colorectal cancer liver metastases. The most common changes linked to oxaliplatin are sinusoidal dilatation and vascular injury that may precede the ultimate development of nodular regenerative hyperplasia and noncirrhotic portal hypertension. The histological changes have little clinical significance, but progression to nodular regenerative hyperplasia can result in complications of ascites, variceal hemorrhage and hepatic decompensation. Once chemotherapy is stopped, the histological changes usually regress and nodular regenerative hyperplasia generally improves and rarely progresses. The platinum coordination complexes have other toxicities that are clinically significant and often overshadow the effects on the liver.
List of platinum coordination complexes